Yr Of Age Research Articles

Abstract 45: The Association of Cumulative Systolic Blood Pressure With Cardiovascular Disease: Findings From the Lifetime Risk Pooling Project Cohorts

Background: Blood pressure (BP) is a known risk factor for cardiovascular disease (CVD), but prior studies have predominantly focused on single measurements of BP. Previous studies which have examined longitudinal BP have been mostly limited to a single cohort and have examined BP during older age. Objective: To assess the association of cumulative systolic BP (SBP) in middle age with CVD using individual-level pooled data from 5 US community-based cardiovascular disease cohorts. Methods: Among participants from the Lifetime Risk Pooling Project, we defined the index date as the earliest SBP measurement taken within 45-65 yr of age with ≥2 previous SBP measurements during the prior 5 years. Multivariate Cox proportional hazards models, with and without current SBP, were used to assess the association of cumulative 5-years SBP (Cum5ySBP, defined as 4 quarters {q1to q4} of SBP mm Hg-years) with any CVD, coronary heart disease, stroke, and heart failure. Models were adjusted for age, sex, race, education, BMI, smoking status, diabetes, total cholesterol level, and use of hypertensive medications as well as index SBP. Results: The association of Cum5ySBP with CVD over an average of 12.9 years was assessed for 13,957 individuals (54.6% women; mean age: 59.6 yr). Cum5ySBP was significantly associated with CVD incidence, with higher risk as the Cum5ySBP increased {Cum5ySBP: HRq2: 1.34 (1.20-1.48), HRq3: 1.71 (1.55-1.90), and HRq4: 2.16 (1.95-2.40)} (Figure 1A). The Cum5ySBP remained significant even when index SBP was incorporated into the model {Cum5ySBP: HRq2: 1.12 (1.01-1.25), HRq3: 1.24 (1.10-1.39), and HRq4: 1.19 (1.03-1.37)} (Figure 1B), as well as when evaluated separately for each type of CVD event. Conclusions: Cum5ySBP is a significant risk factor of CVD, above and beyond current BP. The risk for any CVD component increased with increases in cumulative SBP. These findings emphasize the importance of early treatment for individuals with high BP in order to reduce the cumulative burden of SBP and ultimately prevent CVD outcomes.

Influence of an immune-modulatory feed supplement on performance and immune function of beef cows and calves preweaning.

The ability to positively alter immune and stress response with nutritional compounds is of great interest and importance to the beef industry. There is a proprietary product (OmniGen-AF [OG]; Phibro Animal Health, Quincy, IL) reported to have performance-enhancing benefits by altering animal response to stress and immune challenges. The objective of this 2-yr research project was to study the effect of supplementing OG to beef cows and their calves on breeding and growth performance. One hundred and twelve multiparous beef cows and 48 primiparous cows were randomly assigned to treatment in year 1; control (CON, no OG; n = 56 multiparous and 24 primiparous) or treatment (OG fed at 8.8 g/100 kg body weight [BW]; n = 56 multiparous and 24 primiparous). Multiparous cows (mean ± SD = 6.4 ± 0.4 yr; BW = 589 ± 9.2 kg; body condition score [BCS] 6.2 ± 0.07) were used in both years of the experiment and primiparous cows (mean ± SD = 2.1 ± 0.04 yr of age, weighed 400 ± 7.5 kg, and BSC of 5.6 ± 0.06) were only used in the first year of the experiment. CON and OG supplements were offered over two production cycles beginning in December approximately 60 d prior to projected calving through pre-breeding in May of each year. Calves from treatment cows were offered treatments in a creep supplement limited to a daily rate of 1% as-fed of BW prorated for 3-d/wk feeding from mid-July through weaning with OG offered at 8.8 g/100 kg BW. Primiparous cow's BW, BCS, and calf performance were not affected by treatment (P ≥ 0.15) in year 1. BW of multiparous OG cows tended (P = 0.10) to be heavier at weaning in year 1 and was greater (P = 0.05) at the onset of the experiment in year 2. Body condition of OG cows was greater (P ≤ 0.02) at weaning in both years 1 and 2, as well as at the onset of the experiment in year 2. Calves fed OG from the mature cows gained more (P = 0.05) BW during the creep feeding period than CON. Core body temperatures of OG heifers measured during the late summer with intravaginal temperature data loggers tended (P ≤ 0.10) to be less at 1400 and 1700 hours and were less (P = 0.05) at 1800 hours than CON heifers. Feeding OG did not result in changes (P = 0.25) in serum titer response to the BVD virus of calves during year 2. The results of the current experiment indicate feeding OG to beef cows and calves can result in improvement in BCS of cows, enhance weight gain of calves preweaning, and reduce heat loads in heifer calves during the late summer.

Minimal change in structural, functional and inflammatory markers of lung disease in newborn screened infants with cystic fibrosis at one year

BackgroundWith the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age. MethodsInfants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs. Results65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0–1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4–1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT. ConclusionsIn this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes.

A comparison of clinical outcomes and transplant complications/morbidity with early (

A comparison of clinical outcomes and transplant complications/morbidity with early (<4 months of age) versus late (~ 1 yr of age) hematopoietic stem cell transplant in sibling pairs with a diagnosis of MPS I (Hurler syndrome)

Childhood obesity: rapid weight gain in early childhood and subsequent cardiometabolic risk.

.Dynamic changes in body weight have long been recognized as important indicators of risk for human health. Many population-based observational studies have shown that rapid weight gain during infancy, including a catch-up growth phenomenon or adiposity rebound in early childhood, predisposes a person to the development of obesity, type 2 diabetes, and cardiovascular diseases later in life. However, a consensus has not been established regarding which period of weight gain contributes to future risks. This review evaluates recent evidence on the relationship between early rapid growth and future obesity and cardiometabolic risk, with a focus on the differential significance of rapid weight gain in infancy and early childhood. Although there is a need for attention to childhood growth during early infancy before 1 yr of age as it may be related to future obesity, emerging evidence strongly suggests that toddlers showing an increase in body mass index (BMI) before 3 yr of age, a period normally characterized by decreased BMI, are prone to developing later cardiometabolic risk.

Exercise Intensity and Recovery on Circulating Brain-derived Neurotrophic Factor.

Brain-derived neurotrophic factor (BDNF) is an exercise-induced neurotropin mediating neuroprotection and synaptic plasticity. Although exercise intensity is implicated as a potentially important mediator of BNDF release after exercise, the optimal exercise stimulus (interval vs continuous) and intensity (submaximal vs supramaximal) for augmenting circulating BDNF levels remains unknown. Irisin, an exercise-driven myokine, may also contribute to neuroprotection by upregulating BDNF. To examine the response and recovery of plasma BDNF and irisin after acute exercise of differing intensities. Eight males (23.1 ± 3.0 yr of age; V˙O2max 51.2 ± 4.4 mL·kg·min) completed four acute exercise sessions: 1) moderate-intensity continuous training (MICT, 65% V˙O2max); 2) vigorous-intensity continuous training (VICT, 85% V˙O2max); 3) sprint interval training (SIT, "all out"); and 4) no exercise (CTRL). Blood was collected preexercise as well as immediately, 30 min, and 90 min postexercise. Plasma BDNF and irisin were assessed with commercially available enzyme-linked immunosorbent assay kits. Plasma BDNF levels increased immediately after exercise in the SIT group (P < 0.0001) with plasma concentrations recovering 30 and 90 min postexercise. The BDNF levels after MICT were reduced 30 min postexercise compared with immediately postexercise (P = 0.0189), with no other changes across time points in MICT and VICT groups. Plasma BDNF area under the curve in SIT was significantly higher compared with CTRL, MICT, and VICT (P = 0.0020). No changes in plasma irisin across exercise groups and time points were found (P > 0.9999). Plasma BDNF levels increased in an intensity-dependent manner with SIT eliciting the highest BDNF concentration immediately postexercise. These results identify SIT as a time-efficient exercise modality to promote brain health through BDNF release.

PSIII-29 Effects of late gestational tall fescue forage system on spring-calving beef cow performance, circulating metabolites, and colostrum quality

Abstract Multiparous cows [n = 56; 639 ± 73 (SD) kg initial BW; 5.3 ± 0.4 initial BCS; 5.9 ± 3.0 yr of age; February 16, 2016 average calving date] were allocated by BW, BCS, age, and expected calving date to strip-graze endophyte-infected stockpiled tall fescue (STF; n = 4 pastures; 12.5% CP, 59.5% NDF; DM basis) or consume ad libitum endophyte-infected tall fescue hay (n = 4 uncovered drylots; 7.5% CP, 65.3% NDF; DM basis) for the last 75.0 ± 11.9 d of gestation. At 13.5 ± 1.6 d pre-calving, STF cows were moved to drylots and fed tall fescue haylage (12.6% CP, 61.7% NDF; DM basis). Effects of forage system were included in the model with pen as experimental unit. For gestational metabolites, effects of forage system, day, and their interaction were included with day as a repeated measure. Forage system did not affect (P ≥ 0.35) cow BW. Cows fed STF had greater (P ≤ 0.06) BCS than hay-fed cows at d 32 and 62 of study. Forage system did not affect (P ≥ 0.12) gestational plasma glucose or triglycerides. Serum non-esterified fatty acids (NEFA) were greater (P ≤ 0.005) in hay-fed cows at d 32 and 82 of study and less (P = 0.02) at d 62 of study. After study initiation, serum urea N was greater (P ≤ 0.002) in STF-fed cows than hay-fed cows. At colostrum sampling (6.8 ± 0.9 h postpartum), forage system did not affect (P ≥ 0.10) circulating NEFA, glucose, or triglycerides. Cows fed STF had greater (P ≤ 0.002) serum and colostrum urea N than hay-fed cows. Forage system did not affect (P ≥ 0.17) colostrum protein, lactose, triglyceride, or immunoglobulin concentrations. In conclusion, grazing STF improved cow BCS and altered cow metabolic status but did not affect colostrum quality.

PSVIII-39 Genome-wide DNA methylation alteration in prenatally stressed Brahman heifer calves with the advancement of age

Abstract This study investigated whether DNA methylation patterns changed over the first five yr of life within prenatally stressed (PNS) heifer calves compared to change within a Control group. Prenatal stress was induced by the transportation of pregnant Brahman cows for 2-hr periods at 60±5, 80± 5, 100±5, 120±5, and140±5d of gestation. White blood cells were sampled from the same 6 PNS heifer calves and 8 Control heifer calves at 28 d and 5 yr of age. The DNA methylation data were generated through Reduced Representation Bisulfite Sequencing. Based on results of mapping and bioinformatics analyses, 73,758 hypermethylated and 73,367 hypomethylated CpG sites, 375 hypermethylated and 377 hypomethylated CHG sites, 735 hypermethylated and 842 hypomethylated CHH (C = cytosine; G = guanine; H = either adenine, thymine, or cytosine) sites were obtained from 28-d-old PNS calves compared to when they had matured into 5-yr-old PNS cows (P ≤ 0.05). The 28-d-old Control heifer calves contained 53,005 hypermethylated and 57,103 hypomethylated CpG sites, 200 hypermethylated and 202 hypomethylated CHG sites, 439 hypermethylated and 535 hypomethylated CHH sites compared to when they matured into 5-yr-old Control cows (P ≤ 0.05). As DNA methylation of gene promoter regions is associated with reduced transcription activity, strongly hypermethylated and hypomethylated CpG sites located in promoter regions underwent Ingenuity Pathway Analysis. The top canonical pathways altered by strongly hypermethylated and hypomethylated CpG sites between 28-d-old and 5-yr-old PNS cows were 4-1BB Signaling in T Lymphocytes (P = 0.00169) and Transcriptional Regulatory Network in Embryonic Stem Cells (P = 0.000744). Mineralocorticoid Biosynthesis (P = 0.00901) and Transcriptional Regulatory Network in Embryonic Stem Cells (P = 0.000804) were the other top canonical pathways altered between 28-d-old and 5-yr-old Control cows. PNS calves appeared to develop an altered epigenome compared to Control group calves during the first five yr from birth.

PSX-8 Effects of hair sheep breed and region of origin on feed dry matter required for maintenance without and with a marked feed restriction

Abstract Effects of hair sheep breed and region of origin on feed required for maintenance without and with a substantial restriction were determined with 46 Dorper, 47 Katahdin, and 41 St. Croix females (initial BW of 62, 62, and 51 kg, respectively, SEM=1.43; 3.8±0.18 yr of age, 1.2–11.7) from 45 commercial farms in midwest, northwest, southeast, and central Texas regions of the USA. A 50% concentrate pelleted diet was fed, with the amount varied in the first 4 wk for stable BW and average DM intake in wk 3–4 relative to BW0.75 considered DM required for maintenance without restriction (DMm-m). Feed offered in wk 6–10 was 55% of DMm-m, with DM intake relative to BW0.75 in wk 9–10 considered the requirement with feed restriction (DMm-r). Region had little effect on any measure. The DMm-m was slightly greater (P &amp;lt; 0.05) for St. Croix than for Dorper and Katahdin (49.4, 48.9, and 50.9 g/kg BW0.75 for Dorper, Katahdin, and St. Croix, respectively; SEM=0.48). The decline in BW during the restriction phase was relatively small and similar among breeds (wk 9–10 vs. 3–4: 3.6, 3.2, and 2.9 kg for Dorper, Katahdin, and St. Croix, respectively; SEM=0.21). The DMm-r averaged 43% less than DMm-m, again being greater (P ≤ 0.056) for St. Croix than for Dorper and Katahdin (28.3, 27.9, and 29.1 g/kg BW0.75 for Dorper, Katahdin, and St. Croix, respectively; SEM=0.28). The DMm-m and DMm-r were highly related, indicating that animals would rank similarly at both levels of intake, and variation was similar among breeds. In conclusion, the amount of feed required for BW maintenance was greatest for St. Croix regardless of feed restriction, but differences were minor. The hair sheep exhibited considerable capacity for decreasing the feed requirement for maintenance when offered feed was markedly restricted.

Epidemiological Features of Human Brucellosis in Iran (2011-2018) and Prediction of Brucellosis with Data-Mining Models.

Brucellosis is known as the major zoonotic disease. We aimed to compare the performance of some data-mining models in predicting the monthly brucellosis cases in Iran. Population-based cohort study. Three data mining techniques including the Support Vector Machine (SVM), Multivariate Adaptive Regression Splines (MARS), and Random Forest (RF) besides to one classic model including Auto-Regressive Integrated Moving Average (ARIMA) was used to predict the monthly incidence of brucellosis in Iran during 2011-2018. We used several criteria (root mean square error (RMSE), mean absolute error (MAE), coefficient of determination (R2) and intra-class correlation coefficient (ICC) for appraising the accuracy of prediction and performance of our models. All analysis was done using free statistical software of R3.4.0 RESULTS: Overall 118867 cases (with a mean age of 34.01±1.65 yr) of brucellosis were observed and seven-year incidence rate of brucellosis in Iran was 21.78 (95% CI: 21.66, 21.91). The majority of patients (58.84%) were male and 25-29 yr old. The first three provinces with the highest incidence rate of brucellosis included the following; Kurdistan (71.39 per 100000), Lorestan (68.09 per 100000) and Hamadan (56.24 per 100000). Brucellosis was more common in males, 25-29 aged yr, western provinces and spring months. The disease had a decreasing trend in the last years. MARS model was more appropriate rather than data mining models for prediction of monthly incidence rate of brucellosis.

Stability of genetic predictions for stayability using random regression models that include end points beyond 6 yr of age.

Stability of genetic predictions for stayability using random regression models that include end points beyond 6 yr of age.

Lifetime Sex‐Specific Moose Mortality During an Intentional Population Reduction

ABSTRACTWhere elevated harvest of ungulates is a priority, managers benefit by understanding how various sources of mortality affect the age and sex structure and trend of ungulate populations. Prior studies reported a long period (1997–2014) of moose (Alces alces gigas) nutritional stress from overabundance in our study area, an intentional 31% reduction in moose numbers using liberal harvests of females (2004–2012), and low bear (Ursus spp.) predation and high moose harvest densities relative to other largely roadless systems with moose, bears, and wolves (Canis lupus). In this paper, we detailed management findings after describing causes and rates of mortality from 226 female and 164 male moose radio‐collared at 9 months of age (1997–2008) and followed through life (1997–2019) and throughout the population reduction. We listened for mortality signals on radio‐collars 1–2 times/month when snow cover was complete and 2–4 times/month when snow cover was incomplete. Upon hearing a mortality signal, we investigated mortality sites usually within 24 hours via helicopter. Excluding hunter‐caused mortality, we estimated 28% annual mortality for male yearlings versus 17% for female yearlings, then low annual mortality rates (0–4%) to 84 months of age for males and 96 months of age for females, and gradually increasing annual mortality rates thereafter. Most (83%) male moose ≥24 months of age died from hunters; minor causes included wolves (8%), malnutrition or disease (5%), grizzly bears (U. arctos; 2%), and accidents (2%). Most female moose ≥24 months of age died from wolves (37%) or hunters (33%); minor causes included malnutrition or disease (15%), grizzly bears (10%), and accidents (5%). The proportion of radio‐collared females killed by hunters varied depending on numbers of permits issued to hunters; the kill rate of females ≥24 months of age was 58% during the initial 4 years of the 9‐year reduction, moderated at 29% during the final 5 years of the reduction, and was only 7% for all other study years. We attributed 32% of hunter kills to illegal harvest and unrecovered hunter kills. Hunters played a key role in the intentional population reduction by harvesting prime‐age and near prime‐age male and female moose that rarely died from other sources of mortality compared with calf, yearling, and older moose. Restricting general season hunters to primarily harvesting prime‐age and older male moose with antler spreads ≥127 cm did not appreciably reduce harvest of adult males. Male moose 2.0–5.3 years of age rarely died from non‐hunter causes and were largely harvested at older, prime ages (5.3–8.3 yr of age). Yearling moose of both sexes died primarily from wolves, with wolves selecting more for males. By using liberal harvests of female moose to reduce the population, managers improved moose nutrition and reproduction, met mandates for elevated harvests, and may have avoided a reoccurrence of a previous precipitous decline in moose numbers that was initiated by overabundance and extreme snow depths. © 2019 The Wildlife Society.

Congenital Dyserythropoietic Anemia Type I Due to Biallelic CDAN1 mutations: Report from the Congenital Dyserythropoietic Anemia Registry (CDAR)

Congenital dyserythropoietic anemias (CDA) are rare hereditary diseases of abnormal erythropoiesis. The CDA Registry of North America (CDAR) (NCT02964494) was opened in 2016 to investigate the natural history and molecular biology of CDA. CDA type I (CDA-I) is a recessive form of CDA characterized by macrocytic anemia, hemolysis with inadequate reticulocytosis, and iron overload. The bone marrow shows binucleated erythroblasts with chromatin bridges by light microscopy and spongy heterochromatin in erythroblasts by electron microscopy. The phenotypic heterogeneity in presentation and course of CDA-I is remarkable. Most CDA-I cases are caused by biallelic mutations in CDAN1or C15orf41, and 10-20% do not have an identifiable mutation. Non-hematological features, especially skeletal features, were historically reported in 10-20% of patients (Wickramasinghe, 1998). Due to the rarity of CDA-I and its clinical overlap with several disorders, the diagnosis is often missed or delayed by up to 17 yrs (median) (Roy, 2019). We describe in this study the characteristics and clinical course of CDA-I patients due to CDAN1 mutations enrolled in CDAR. Patients with a phenotypic diagnosis of CDA and their family members were enrolled in CDAR. Clinical and demographic data were gathered from participants at study entry and updated periodically thereafter. Participants elect to give blood, bone marrow, and DNA samples to the biorepository associated with CDAR. Participants with a phenotypic diagnosis of CDA-I and confirmed mutations in CDAN1 were included in this study. Six participants had a diagnosis of CDA-I due to biallelic CDAN1 mutations, comprising 18% (6/33) of affected CDAR participants. CDAN1 mutations were found in 75% of cases diagnosed phenotypically as CDA-I. All six participants presented early in life with a variable degree of non-immune hemolysis, and the diagnosis was confirmed within a median of 2 years from presentation. The characteristics of participants are summarized in table 1. Two had family history of stillbirth or fetal demise in older siblings due to hydrops fetalis. One participant presented prenatally with fetal anemia and started intrauterine transfusions at 24 weeks of gestation; 2 presented with severe anemia and signs of hydrops, pulmonary hypertension, transaminitis, severe hyperbilirubinemia, and thrombocytopenia at birth; and 3 presented with neonatal jaundice and moderate anemia. All participants required blood transfusions in the neonatal period. Three had spontaneous improvement and did not require transfusions after the first year of life. One remained transfusion-dependent at last follow up at the age of 4 yrs. One became transfusion-independent after starting interferon-alpha at 1 yr of age and did not need further transfusions even after discontinuation at 3 yrs of age. One had splenectomy at 11 y.o because he was misdiagnosed to have a membrane disorder but presented in adulthood with hemolytic anemia and pulmonary hypertension and was diagnosed at that time with CDA-I by genetic sequencing. All participants had one or more non-hematological manifestations, including hypertrophic skin folds, onychocryptosis, curved toenails, syndactyly, café-au-lait spots, macrocephaly, spinal fusion, scoliosis, and short stature. One participant suffered a thalamic stroke in the postnatal period, 2 had transient neonatal pulmonary hypertension in the setting of severe anemia, and one had pulmonary hypertension post-splenectomy in adulthood. Ferritin was high in all participants at last follow up, and 4 received chelation therapy. In summary, mutations in CDAN1 are the most common identified mutations in CDAR. CDA-I causes early-onset macrocytic anemia, which may present prenatally, with variable severity of hemolysis ranging from hydrops to mild neonatal jaundice and anemia. Non-hematological manifestations, mainly skeletal, nail and skin abnormalities are more common in CDA-I than previously reported, and their presence in infants with unexplained anemia should raise suspicion for the diagnosis. The availability of molecular testing has significantly accelerated the diagnosis. Management of patients with CDA-I requires multidisciplinary approach from an early age to improve outcome. Collaboration between clinicians, scientists, patients, and families is needed to advance the understanding and treatment of this rare disease. Disclosures Chonat: Alexion: Other: advisory board; Agios Pharmaceuticals, Inc.: Other: advisory board. Kalfa:Agios: Other: local PI of clinical research trial; FORMA: Other: sponsored research agreement.

Neutrophil Extracellular Traps (NETs) Are a Subset of Smudge Cells Identifiable By Peripheral Smear Autoanalyzers

Background. Neutrophil Extracellular Traps (NETs) are composed of extracellular decondensed chromatin networks that play an important role in immune and inflammatory response regulation. Simple and reliable identification of NETs has been challenging. Automated analyzers such as the CellaVision® Hematology Autoanalyzer identify a subset of cell-derived entities as smudge cells. We hypothesize that, in addition to the typical degenerated lymphocytes (DLs) forming smudge cells, a proportion of smudge cells as identified by the Autoanalyzer are actually NETs. Since patients with high numbers of NETs have increased and specific morbidities, accurate and rapid identification of NETs may be clinically useful. Methods. To test our hypothesis, we analyzed peripheral blood smears from samples processed by the CellaVision® Hematology Autoanalyzer. To differentiate NETs from DLs we used morphologic characteristics, immunohistochemistry, and flow cytometry. After immunohistochemistry and flow cytometry informed our morphologic classification of NETs and DLs, we relied solely on morphology. Smears with &gt;20% smudge cells were classified as the study group; the control group had &lt; 5% smudge cells. Medical chart review was performed by investigators blinded to sample group designation. Data obtained from chart review included patient demographics; presence of bacterial and/or viral infection occurring &lt;1 week of sample collection; myeloproliferative and lymphoproliferative disorders (LPD); solid organ malignancy and/or transplant; sickle cell disease; chronic kidney (CKD) and liver diseases; autoimmune disorders; HIV; thrombotic events. We reviewed the same sample laboratory data for hemoglobin, platelet counts, and white blood cell (WBC) counts. Statistical analyses were performed using two-sided t-test with α =0.05 for continuous variables, chi-square for categorical variables with samples size &gt;10 and Fisher's exact tests for categorical variables with sample size &lt;10. Results. 155 samples were used in the analysis: 96 in the study group, 59 in the control group. Cell-derived entities staining strongly with myeloperoxidase (MPO), neutrophil elastase (NE), and leukocyte alkaline phosphatase (LAP) were classified as NETs. On flow cytometry, these NETs are at least twice as large as WBCs, display extracellular DNA (as identified by Sytox dye) and stain positively for MPO [Figure 1]. On Wright-Giemsa stain, these appeared morphologically as cell remnants with decondensed nuclei, no intact cytoplasm, dispersed granules, and polarized chromatin projections that resemble spider webs [Figure 2]. Of 96 patient samples with &gt;20% smudge cells, morphologic analyses designated 88 as NETs and only 8 as DLs. Comparing patients with &gt;20% to &lt;5% total smudge cells, the former had a higher incidence of bacterial infections (p=0.0091), as well as higher WBC, lymphocyte, monocyte counts and hemoglobin (p=0.014, 0.009, 0.004, 0.01 respectively) [Table 1]. High percentage of smudge cells correlated with a higher percentage of bacterial infection when compared to those with fewer smudge cells despite a non-significant difference in total neutrophil counts. Only 3 of the 36 patients with documented bacterial infection in the &gt;20% smudge cell group had a neutrophils &gt;8.5 x109/L. Of 13 infants &lt;1yr of age with &gt;20%smudge cells, 5 had a bacterial infection with normal neutrophil counts. When the smudge cells were separated according to their category, NETs vs DLs, the DL group was older, had more LPD, higher total WBC, lymphocyte and monocyte counts (p=0.000044, 0.00036, 0.018, 0.022, 0.033) [Table 2]. Slides with mostly NETs had higher LAP scores than those classified as mostly DLs (172 +30.5 vs 103.3 +30.8, p=0.0087). Conclusions: NETosis is a relatively newly discovered tool in the neutrophil's arsenal. This study is the first to identify NETs on peripheral smear evaluations as performed by a routine Hematology Autoanalyzer and to differentiate them from DLs using a reliable set of morphologic characteristics, immunohistochemical stains, and flow cytometry probes. This study also supports data that associate NETs with bacterial infections. This could be clinically useful in diagnosis of infection in the absence of leukocytosis. Disclosures Billett: Albert Einstein College of Medicine: Patents &amp; Royalties: Patent application pending for NETs AI software. Kushnir:Janssen Pharmaceuticals: Research Funding. Reyes Gil:Albert Einstein College of Medicine: Patents &amp; Royalties: Patent application pending for NETs AI software.

Impact of menopausal hormone formulations on pituitary-ovarian regulatory feedback.

Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of postmenopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45 ± 2.49 yr of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE; n = 109), transdermal 17β-estradiol (t-E2; n = 107), or placebo (n = 146). Androstenedione, testosterone, 17β-estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum before (baseline) and 48 mo after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE, t-E2, and placebo on these hormone levels at 48 mo, adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 mo within treatment groups. As expected, at 48 mo of treatment, hormone levels differed between women in the two active treatment groups compared with placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups compared with placebo. Associations among testosterone, 17β-estradiol, FSH, and LH differed between the o-CEE group compared with t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and interhormonal associations in recently menopausal women. These interactions provide the basis for future studies investigating the impact of hormonal modulation of aging, including cognitive decline in women.

Alphabet problems linked with learning disability in children: a cross sectional study

Background: Learning Disability (LD) is a frequently neglected entity in our set up, with the affected children being labeled as dull and worthless. The feeling of inadequacy and shame leads to psychological problems in approx. 30% of these children. These include low self-esteem, school phobia, anxiety, depression, oppositional-defiant behavior and conduct disorders. Early recognition of this disability in the primary school children and initiating appropriate remedial measures can significantly reduce morbidity. Authors objective was to study the prevalence and pattern of alphabet problems in children with learning disability.Methods: This was a cross sectional study done in the Child Guidance Clinic of a tertiary care teaching hospital in Chitradurga district, Karnataka, between January 2016 and January 2018. After obtaining informed consent from parents, children between ages 5 to 17 years, diagnosed to have learning disability, were asked to write upper and lower case alphabets in English. Alphabet problem was diagnosed if child had mixing of upper and lower case alphabets, missing of alphabets, reversals and improper sequence. Association of alphabet problems with age and sex was studied.Results: There were 293 children with learning disability, between 5-17 yr of age, attending our Child Guidance Clinic, who were assessed for alphabet problems. Alphabet problems were noted in 83.6% children. Mixing of upper and lower case alphabets was seen in 74.74%, missing of alphabets in 25.94%, reversal of alphabet in 21.50% and errors in sequencing in 12.97%. The prevalence of alphabet problems was higher in the 5-8yr age group. Prevalence of alphabet problems was more in males compared to females.Conclusions: Alphabet problems were present in a significant number of children with learning disability. Presence of alphabet problems could be used as a simple screening tool for children with learning disabilities.

Assessment of Common Criteria for Awake Extubation in Infants and Young Children.

Practice patterns surrounding awake extubation of pediatric surgical patients remain largely undocumented. This study assessed the value of commonly used predictors of fitness for extubation to determine which were most salient in predicting successful extubation following emergence from general anesthesia with a volatile anesthetic in young children. This prospective, observational study was performed in 600 children from 0 to 7 yr of age. The presence or absence of nine commonly used extubation criteria in children were recorded at the time of extubation including: facial grimace, eye opening, low end-tidal anesthetic concentration, spontaneous tidal volume greater than 5 ml/kg, conjugate gaze, purposeful movement, movement other than coughing, laryngeal stimulation test, and oxygen saturation. Extubations were graded as Successful, Intervention Required, or Major Intervention Required using a standard set of criteria. The Intervention Required and Major Intervention Required outcomes were combined as a single outcome for analysis of predictors of success. Successful extubation occurred in 92.7% (556 of 600) of cases. Facial grimace odds ratio, 1.93 (95% CI, 1.03 to 3.60; P = 0.039), purposeful movement odds ratio, 2.42 (95% CI, 1.14 to 5.12; P = 0.022), conjugate gaze odds ratio, 2.10 (95% CI, 1.14 to 4.01; P = 0.031), eye opening odds ratio, 4.44 (95% CI, 1.06 to 18.64; P= 0.042), and tidal volume greater than 5 ml/kg odds ratio, 2.66 (95% CI, 1.21 to 5.86; P = 0.015) were univariately associated with the Successful group. A stepwise increase in any one, in any order, of these five predictors being present, from one out of five and up to five out of five yielded an increasing positive predictive value for successful extubation of 88.3% (95% CI, 82.4 to 94.3), 88.4% (95% CI, 83.5 to 93.3), 96.3% (95% CI, 93.4 to 99.2), 97.4% (95% CI, 94.4 to 100), and 100% (95% CI, 90 to 100). Conjugate gaze, facial grimace, eye opening, purposeful movement, and tidal volume greater than 5 ml/kg were each individually associated with extubation success in pediatric surgical patients after volatile anesthetic. Further, the use of a multifactorial approach using these predictors, may lead to a more rational and robust approach to successful awake extubation.

CLINICAL CONDITIONS FOUND RADIOGRAPHICALLY IN THE FRONT FEET OF RETICULATED GIRAFFE (GIRAFFA CAMELOPARDALIS RETICULATA) IN A SINGLE ZOO.

Front foot radiographs from 22 giraffe (Giraffa camelopardalis reticulata) at one zoo were analyzed to better understand causes of lameness in this giraffe population. The herd had a history of front hoof overgrowth and intermittent lameness. Radiographic findings included distal interphalangeal joint osteoarthritis (OA), distal phalangeal bone (P3) osteitis, P3 fractures, P3 rotation, and sesamoid bone cysts. OA of the distal interphalangeal joint occurred in at least one front foot of 73% (16/22 giraffe) of the herd, and all giraffe had OA by 7 yr of age. Pedal osteitis was present in at least one front foot in 86% (19/22) of the giraffe, starting in animals as young as 1 yr old. P3 fractures were present in 36% (8/22) of the herd. These fractures were near the site of the deep digital flexor attachment and were diagnosed in giraffe as young as 10 yr old. The presence of severe osteitis was associated with the presence of P3 fractures. This study is unique in that a large herd was trained to participate in voluntary front foot radiographs so multiple causes of foot disease could be diagnosed antemortem and without anesthesia. Although the underlying causes of these lesions are likely multifactorial and currently unknown to us, the high prevalence of foot disease in relatively young animals warrants further investigation across zoos. In this study, OA, osteitis, and P3 fractures were common radiographic findings among giraffe that were limping. Subsequent monitoring and management changes suggest that proactive management of foot health can decrease morbidity and mortality in zoo giraffe.

Comparing Radiographic Parameters for Single-Level L5-S1 Interbody Fusion: Anterior Lumbar (ALIF) Versus Transforaminal Lumbar Interbody Fusion (TLIF)

Abstract INTRODUCTION The lumbosacral junction acts as a transition point between the mobile lumbar spine and the rigid pelvis. It is thereby susceptible to degenerative changes necessitating fusion at L5-S1. In this study, we compared radiographic outcomes observed from single-level anterior lumbar interbody fusion (ALIF) and transforaminal lumbar interbody fusion (TLIF) at this level. METHODS Retrospective review of single-level ALIF and TLIF with up to one level PSF at L5-S1 between May 2007 and October 2018 was undertaken. X-ray measurements were gathered for lumbar lordosis, segmental lordosis, pelvic tilt, sacral slope, pelvic incidence, pelvic incidence-lumbar lordosis mismatch, anterior/posterior disc height, and sagittal vertical axis. Computed tomography /magnetic resonance imaging was used to determine central canal area, sagittal diameter, foraminal height, and foraminal area. RESULTS A total of 47 ALIF patients and 50 TLIF patients were included. Patients averaged 53.7 ± 10.1 yr of age for ALIF and 49.4 ± 14.7 yr old for TLIF (P = .094) with significant differences (P = .0017) seen with gender as ALIF had 60.4% males and TLIF 70.0% females. Single-level ALIF led to significantly (P = .0010) more segmental lordosis (+5.75° ± 7.31°) than TLIF (+0.25° ± 6.55°), though differences in lumbar lordosis were not statistically significant (P = .52). ALIF significantly increased both anterior (+10.4 ± 4.32 mm vs +4.30 ± 3.55 mm; P &lt; .0001) and posterior disc height (+4.33 ± 3.32 mm vs + 2.98 ± 2.07 mm; P = .043) than TLIF. Changes in sagittal vertical axis also significantly differed (P = .030) with ALIF decreasing sagittal vertical axis by 17.8 ± 26.4 mm from +60.3 mm to + 42.5 mm, and TLIF increasing by 0.95 ± 25.8 mm from 39.9 mm to 40.9 mm. Pelvic tilt, sacral slope, pelvic incidence, pelvic incidence-lumbar lordosis mismatch had no significant differences. No statistically significant differences were observed with central canal area, sagittal diameter, foraminal height or foraminal area between ALIF and TLIF. CONCLUSION At L5-S1, the ALIF approach leads to increased segmental lordosis, disc height, while also decreasing sagittal vertical axis to a significant degree than TLIF. However, these two approaches were no different with regards to pelvic parameters and measures of central canal and foraminal decompression.

Clinical and Imaging Outcomes After Combined Direct and Indirect Bypass for Pediatric Moyamoya Disease: A Single Center Retrospective Series

Abstract INTRODUCTION Moyamoya disease is a progressive cerebrovascular arteriopathy of unknown etiology, causing narrowing and eventual occlusion of the internal carotid arteries and their branches. Surgical revascularization is a key component of the overall treatment strategy. The goal of this study was to determine outcomes and complications related to direct vascular bypass in a pediatric cohort with Moyamoya disease. METHODS All pediatric patients (&lt;18 yr of age) treated with direct bypass combined with encephalomyosynangiosis between 2006 and 2017 at the authors’ institution were included in the cohort. Demographic features, treatment, and outcomes were determined retrospectively from clinical reports available through the electronic medical record. RESULTS A total of 18 patients (11 females and 7 males) underwent 32 bypass procedures with a median follow-up of 2.2 yr (range 22 d 8.6 yr). Mean age at operation was 8.3 yr (range 1.4-16.9 yr). Preoperative Suzuki stage 1, 2, 3, 4, and 5 were seen in 2, 7, 7, 12, and 4 hemispheres, respectively. By last follow-up, 3 patients had evidence of new clinical ischemic stroke, all occurring within 30 d of surgery. Favorable outcomes (pediatric modified Rankin scores 0-2) at last follow-up were seen in 15 patients (83.3%). There was 1 death in the cohort due to gastrointestinal bleeding related to underlying medical comorbidities. On review of imaging at last follow-up for surviving patients, 29 of 30 direct arterial bypasses were patent; 12 and 5 patients had stable and worse imaging findings, respectively, when compared to immediate postoperative scans. CONCLUSION Combined direct and indirect revascularization procedures may be successfully applied to pediatric patients with Moyamoya disease of all age groups. The direct bypass component provides immediate revascularization and is associated with high rates of patency on follow-up imaging.